Here, we report the pediatric cases of sitosterolemia, a rare autosomal-recessive genetic disorder, characterized by high concentrations of plant sterols in blood and heterogeneity manifestations. All three patients (two girls aged 2 and 6 years old, and one boy aged 14 years old) were initially diagnosed with hypercholesterinemia. Next-generation sequencing (NGS) revealed homozygous (p.Leu572Pro/p.Leu572Pro) and compound (p.Leu572Pro/p.Gly512Arg and p.Leu572Pro/p.Trp361*) variants in the ABCG8 gene that allowed for the diagnosis of sitosterolemia. Two patients whose blood phytosterol levels were estimated before the diet demonstrated high levels of sitosterol/campesterol (69.6/29.2 and 28.3/12.4 μmol/L, respectively). Here, we demonstrate that NGS-testing led to the proper diagnosis that is essential for patients’ management. The variant p.Leu572Pro might be prevalent among patients with sitosterolemia in Russia.

In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements.

Sitosterolemia (phytosterolemia) is an inherited metabolic disorder characterized by the accumulation of plant sterols (phytosterols). The disease is caused by loss-of-function genetic mutations in sterolin proteins, which play an important role in selective excretion of plant sterols. Patients exhibit increased serum levels of phytosterols, total cholesterol and low-density lipoprotein cholesterol, which is accompanied by the risk of pre-mature atherosclerosis. Patients can have severe sitosterolemia when xanthomatosis develops as early as in infancy. Hematological disorders in the form of macrothrombocytopenia, stomatocytosis, episodes of hemolysis are reported in patients with sitosterolemia, which can be the only manifestation of the disease and are often interpreted as a manifestation of immune thrombocytopenia or primary hemolytic anemia. Hepatoand splenomegaly, acute liver failure, arthralgia may also be seen. Due to the similarity of clinical phenotypes, sitosterolemia can be misdiagnosed as familial hypercholesterolemia. It is vitally important to perform differential diagnosis to distinguish it from such diseases as lecithin-cholesterol acyltransferase deficiency, Tangier disease, cerebrotendinous xanthomatosis, familial dysbetalipoproteinemia, lysosomal acid lipase deficiency, primary biliary cirrhosis, storage diseases. The treatment of sitosterolemia in children includes the use of the intestinal cholesterol/phytosterol absorption inhibitor ezetimibe and bile acid sequestrant cholestyramine. The effective use of the combination of these drugs is described. The partial bypass of the distal ileum where the absorption of cholesterol, phytosterols, and reabsorption of bile acids mainly occurs can be used in severe cases. For patients with advanced vascular atherosclerosis and resistance to the standard treatments, LDL-C apheresis could be considered. The article describes our own clinical observation of a five-year-old patient suffering from sitosterolemia.

Inherited metabolic disorders have a specific place among cases of sudden deterioration of the newborn’s condition. Therapies have been developed for some of these disorders. Accurate verification of the diagnosis is extremely important for choosing an optimal treatment strategy. However, treatment is not always successful due to the rapid progression of symptoms. We report a case of citrullinemia diagnosed in a newborn in Vidnoye Perinatal Center.